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Project Title:  Impact of Long Duration Space Flight on Cardiac Structure and Function Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 05/01/2010  
End Date: 07/31/2014  
Task Last Updated: 12/24/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Thomas, James David M.D. / The Cleveland Clinic Foundation 
Address:  Cardiovascular Medicine 
9500 Euclid Ave 
Cleveland , OH 44195-0001 
Email: thomasj@ccf.org 
Phone: 216-445-6312  
Congressional District: 11 
Web:  
Organization Type: NON-PROFIT 
Organization Name: The Cleveland Clinic Foundation 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Popovic, Zoran  The Cleveland Clinic Foundation 
Bungo, Michael  The University of Texas Health Science Center at Houston 
Martin, David  NASA Kennedy Space Center 
Greenberg, Neil  The Cleveland Clinic Foundation 
Borowski, Allen  The Cleveland Clinic Foundation 
Levine, Benjamin  The University of Texas Southwestern Medical Center at Dallas 
Kassemi, Mohammad  NASA Glenn Research Center 
Key Personnel Changes / Previous PI: NOTE: PI change to Zoran Popovic, M.D., Ph.D. in August 2014, per NSBRI (Ed., 1/8/15)
Project Information: Grant/Contract No. NCC 9-58-CA02203 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02203 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
Human Research Program Gaps: (1) CV01:What are the in-flight alterations in cardiac structure and function?
Flight Assignment/Project Notes: NOTE: End date changed to 7/31/2014 due to PI change to Zoran Popovic, M.D., Ph.D. in August 2014, per NSBRI (Ed., 1/8/15)

NOTE: Risk/Gap changes per IRP Rev E (Ed., 1/7/14)

Task Description: As astronauts venture farther into space, the impact of long-term microgravity on cardiovascular function may become a critical limitation to mission safety and success. In order to better understand the impact of long-term spaceflight on the structure and function of the heart, the PI is already involved in echocardiographic analysis of the most detailed study of the heart in space ever undertaken. Unfortunately, the echocardiograph on the International Space Station is more than a decade old and does not provide contemporary information on cardiac function, such as strain (the best measure of regional and global contraction of the muscle) and torsion (the twisting motion of the heart that links the pumping and filling functions of the ventricle). Our first task in this proposal is to develop and validate methodology to extract strain and torsion from space station echoes and then combine it with the numerous pre- and post-flight studies that will be conducted over the next four years. From these data, we will have a comprehensive view of the heart in space, information which will be integrated into evolving mathematical models of the heart that the PI and collaborators have developed, and which will be made available to the general NASA community via integration into the Digital Astronaut project. Finally, the PI and colleagues are involved extensively in the development of the next generation of echo machines and have the unique opportunity to develop and validate advanced applications for space use. We will focus on massively parallelized echo machines capable of real-time 3D imaging with automated volume measurements and comprehensive 3D strain and torsion analysis. As these machines become smaller over time, they will provide the ideal diagnostic tool for future space missions, be they to low Earth orbit, a Lagrangian point, the moon, or even Mars.

Exposure to microgravity induces short and long-term changes in the cardiovascular system, with cardiac atrophy, orthostatic hypotension, and impaired thermoregulation being the most recognizable. The most obvious issue, noted in the majority of astronauts after long-term space flight, is orthostatic hypotension. While its importance is clear, the etiology remains uncertain, with proposed mechanisms including hypovolemia, impaired baroreflexes, and left ventricular atrophy leading to systolic and/or diastolic dysfunction.

In order to better define these issues, NASA is currently conducting Flight Study E377, Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capacity, and Risk of Cardiac Arrhythmias (Ben Levine and Mike Bungo, Co-PIs, both of whom are Co-Is on this application). This program is also termed the Integrated Cardiovascular Study, or ICV. As part of this investigation, detailed imaging studies are conducted on astronauts before, during, and after space flight, including an extensive series of in-flight resting and exercise echocardiograms. The PI monitors all in-flight echoes remotely in real-time, and he and his colleagues at the Cleveland Clinic serve as the echocardiographic core lab for this study. We thus are in a unique position to guide on-flight acquisition as well as perform detailed examination of the ultrasound studies received. However, ICV was initially proposed in 1999 with echocardiographic techniques that are now over ten years old, focusing mainly on ventricular size, mass, and simple measures of systolic function, such as ejection fraction and stroke volume. Echocardiography has advanced considerably since then in the sophisticated ventricular mechanical data that can be extracted from ultrasound data.

In the current proposal, we wish to validate extraction of these novel echocardiographic indices of ventricular mechanics (two-dimensional strain and torsion, among others) from the in-flight data acquired on the 10-year-old HDI-5000 ultrasound system aboard the International Space Station, which was never designed to provide such data. Once validated, we will be able to derive detailed regional ventricular mechanics from all of our in-flight studies, allowing direct comparison with the pre- and post-flight examinations to gain a much better understanding of the magnitude and time course of structural and functional changes in the cardiovascular system in microgravity. These enhanced data from ICV will provide the ideal input for mathematical modeling of the cardiovascular system in space. The PI and colleagues have long experience with mathematical modeling ranging from lumped parameter models to 2D structural models to full 3D finite element models. We will apply the structural and strain data from ICV to our evolving numerical models of the cardiovascular system. To model atrophy of the heart, we will use the actual astronaut geometry from pre- and post-flight examinations, to build realistic 3D finite element models. Chamber behavior will be extracted for use in our less computationally intense lumped parameter model. Such modeling will be made available to the NASA community to enhance the comprehensive Digital Astronaut model.

Finally, looking toward a future of long duration missions to the moon and on to Mars, we anticipate that even more sophisticated ultrasound data will be available through the expected commercial development of hand-held three-dimensional echocardiographs. Our group stands in a unique position to capitalize on these developments and to validate their eventual use in the manned space program. For all of these reasons, we believe this proposal is quite responsive to the charge to the Cardiovascular Alterations Team.

Research Impact/Earth Benefits: Several aspects of this project are already generating significant real-world benefits with many more anticipated in the future. Our work attempting to harmonize strain measurements across platforms has pointed out intervendor variability that significantly limits penetration of strain echocardiography into clinical practice. To address this, I have (in my role of President of the American Society of Echocardiography) convened a task force in collaboration with the European Association of Echocardiography and technical representatives from multiple vendors (GE, Siemens, Philips, Toshiba, Esaote, Ziosoft, Zonare, among others). We have proposed a multipronged validation protocol, consisting of synthetic datasets, animal experiments, and clinical validation at upcoming international congresses. In addition, we have engaged the DICOM (Digital Imaging and Communications in Medicine) committee with 2 proposals: 1) development of a new standardized format for storing raw ultrasound data (ideal for strain measurements) and 2) development of standardized nomenclature for advanced mechanics parameters, so analysis packages of the various vendors can communicate their results with each other and between data and picture archives. Additionally, the modeling work being done in Cleveland and Auckland, while designed to allow simulation of the impact of physiological stressors in space flight on the cardiovascular system, will have widespread applicability in cardiology. For example, the user interface developed in Auckland allows any DICOM echocardiogram to be read into the program, segmentation and strain analysis to be performed, and then modeling of that heart using pre-existing fiber models of the ventricle. Once refined and validated, this should allow analysis of patients with regional and global dysfunction, as well as those with valvular heart disease. Work is also underway to allow 3D echoes to be read directly into the interface, including the full strain tensor as reported throughout the 3D space (Toshiba machine). Finally, we have leveraged our work in 3D echocardiographic strain to participate in an international consortium to establish normal values for global and regional 3D strain. 3D echocardiography is undergoing rapid development and this work will help to set normative standards against which clinical acquisitions can be compared.

Task Progress & Bibliography Information FY2013 
Task Progress: Specific Aim 1: Validate strain and torsion data from HDI-5000 data: Due to difference of in-flight and pre/post flight testing systems, test use Velocity Vector Imaging (VVI) to extract strain and torsion from the HDI-5000 data that will agree with data from the same subjects analyzed on an IE-33 system. We have completed a study of 100 subjects at Cleveland Clinic, demonstrating strong correlation (r=0.9) between strain measurements on different platforms.

Specific Aim 2: Quantitative analysis of echo data: compare the temporal evolution of LV volume, mass, and function with echo, MRI, and hemodynamic data. All pre-, post-, and in-flight echocardiographic data obtained for the Integrated Cardiovascular Study (E377) has been measured. Analysis of this data continues, but presentations of interim results have been made on the impact of microgravity on cardiac shape and strain.

Specific Aim 3: Integration of the pre-, in-, and post-flight data into evolving numerical models of the cardiovascular system. (A) In collaboration with the Auckland Bioengineering Institute, an approach for integrated cardiac function modeling and analysis has been developed. A comprehensive computer model of the cardiovascular system was developed specifically for NASA and NSBRI. This model transforms anatomic images of the heart into representations of the myocardial architecture, converting strain in the longitudinal, circumferential, and radial directions into actual myofibril shortening. This framework has been installed at the Cleveland Clinic for cardiac consultant trials.

(B) In collaboration with the National Center for Space Exploration Research (NCSER) at the NASA Glenn Research Center an Orthotropic 3D Finite Element Heart Model is being utilized for the Prediction of Cardiac Gravitational Deformation and Stress Distribution. A finite element model of the heart is developed to investigate the impact of different gravitational loadings of Earth, Mars, Moon, and Microgravity on the cardiac shape and strain/stress distributions in the left ventricle.

Specific Aim 4: Derivation of ventricular mechanics from three-dimensional echocardiography: propose to work closely with emerging three-dimensional echocardiographic units to develop and validate speckle tracking algorithms utilizing three-dimensional data. Investigation on the definition of normal values for 3D strain data is ongoing with an International Consortium with Toshiba Medical. Utilization of Philips 3D native data for post-processing is currently being explored in collaboration with Ivan Salgo (Philips).

Bibliography Type: Description: (Last Updated: 04/09/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Negishi K, Popovic ZB, Greenberg N, Borowaski A, Martin DS, Bungo MG, Levine BD, Thomas JD. "Impact of Spaceflight on intra-ventricular pressure gradient: An interim analysis from the integrated cardiovascular study." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Articles in Peer-reviewed Journals Iskovitz I, Kassemi M, Thomas JD. "Impact of weightlessness on cardiac shape and left ventricular stress/strain distributions." J Biomech Eng. 2013 Dec;135(12):121008. http://dx.doi.org/10.1115/1.4025464 ; PubMed PMID: 24048335 , Dec-2013
Articles in Peer-reviewed Journals Gladding PA, Cave A, Zareian M, Smith K, Hussan J, Hunter P, Erogbogbo F, Aguilar Z, Martin DS, Chan E, Homer ML, Shevade AV, Kassemi M, Thomas JD, Schlegel TT. "Open access integrated therapeutic and diagnostic platforms for personalized cardiovascular medicine." J Pers Med. 2013 Aug 21;3(3):203-37. http://dx.doi.org/10.3390/jpm3030203 ; PubMed PMID: 25562653; PubMed Central PMCID: PMC4251391 , Aug-2013
Articles in Peer-reviewed Journals Negishi K, Borowski AG, Popovic ZB, Greenberg NL, Martin DS, Bungo MW, Levine BD, Thomas JD. "Effect of gravitational gradients on cardiac filling and performance." J Am Soc Echocardiogr. 2017 Dec;30(12):1180-8. https://doi.org/10.1016/j.echo.2017.08.005 ; PubMed PMID: 29056408 , Dec-2017
Awards Iskovitz I, Kassemi M, Thomas JD. "Recipient of the best paper award. 2nd International Conference on Mechanical Engineering and Mechatronics (ICMEM'13), Toronto, Canada, August 9-9, 2013." Aug-2013
Papers from Meeting Proceedings Iskovitz I, Kassemi M, Thomas JD. "Impact of Gravitational and Pressure Loading on Cardiac Shape and Stress/Strain Distributions Using the Finite Element Method." 7th MIT Conference on Computational Fluid and Solid Mechanics: Multiphysics and Multiscale, Cambridge, MA, June 12-14, 2013.

7th MIT Conference on Computational Fluid and Solid Mechanics: Multiphysics and Multiscale, Cambridge, MA, June 12-14, 2013. , Jun-2013

Papers from Meeting Proceedings Iskovitz I, Kassemi M, Thomas JD. "Gravitational Effects on Cardiac Shape and Stress." 2nd International Conference on Mechanical Engineering and Mechatronics (ICMEM'13), Toronto, Canada, August 8-9, 2013.

2nd International Conference on Mechanical Engineering and Mechatronics (ICMEM'13), Toronto, Canada, August 8-9, 2013. Paper 197. , Aug-2013

Project Title:  Impact of Long Duration Space Flight on Cardiac Structure and Function Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 05/01/2010  
End Date: 09/30/2014  
Task Last Updated: 12/19/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Thomas, James David M.D. / The Cleveland Clinic Foundation 
Address:  Cardiovascular Medicine 
9500 Euclid Ave 
Cleveland , OH 44195-0001 
Email: thomasj@ccf.org 
Phone: 216-445-6312  
Congressional District: 11 
Web:  
Organization Type: NON-PROFIT 
Organization Name: The Cleveland Clinic Foundation 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Popovic, Zoran  The Cleveland Clinic Foundation 
Bungo, Michael  The University of Texas Health Science Center at Houston 
Martin, David  NASA Kennedy Space Center 
Greenberg, Neil  The Cleveland Clinic Foundation 
Borowski, Allen  The Cleveland Clinic Foundation 
Levine, Benjamin  The University of Texas Southwestern Medical Center at Dallas 
Kassemi, Mohammad  NASA Glenn Research Center 
Project Information: Grant/Contract No. NCC 9-58-CA02203 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02203 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
Human Research Program Gaps: (1) CV01:What are the in-flight alterations in cardiac structure and function?
Task Description: As astronauts venture farther into space, the impact of long-term microgravity on cardiovascular function may become a critical limitation to mission safety and success. In order to better understand the impact of long-term spaceflight on the structure and function of the heart, the PI is already involved in echocardiographic analysis of the most detailed study of the heart in space ever undertaken. Unfortunately, the echocardiograph on the International Space Station is more than a decade old and does not provide contemporary information on cardiac function, such as strain (the best measure of regional and global contraction of the muscle) and torsion (the twisting motion of the heart that links the pumping and filling functions of the ventricle). Our first task in this proposal is to develop and validate methodology to extract strain and torsion from space station echoes and then combine it with the numerous pre- and post-flight studies that will be conducted over the next four years. From these data, we will have a comprehensive view of the heart in space, information which will be integrated into evolving mathematical models of the heart that the PI and collaborators have developed, and which will be made available to the general NASA community via integration into the Digital Astronaut project. Finally, the PI and colleagues are involved extensively in the development of the next generation of echo machines and have the unique opportunity to develop and validate advanced applications for space use. We will focus on massively parallelized echo machines capable of real-time 3D imaging with automated volume measurements and comprehensive 3D strain and torsion analysis. As these machines become smaller over time, they will provide the ideal diagnostic tool for future space missions, be they to low earth orbit, a Lagrangian point, the moon, or even Mars.

Exposure to microgravity induces short and long-term changes in the cardiovascular system, with cardiac atrophy, orthostatic hypotension and impaired thermoregulation being the most recognizable. The most obvious issue, noted in the majority of astronauts after long-term space flight, is orthostatic hypotension. While its importance is clear, the etiology remains uncertain, with proposed mechanisms including hypovolemia, impaired baroreflexes, and left ventricular atrophy leading to systolic and/or diastolic dysfunction. In order to better define these issues, NASA is currently conducting Flight Study E377, Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capacity, and Risk of Cardiac Arrhythmias (Ben Levine and Mike Bungo, Co-PIs, both of whom are Co-Is on this application). This program is also termed the Integrated Cardiovascular Study, or ICV.

As part of this investigation, detailed imaging studies are conducted on astronauts before, during and after space flight, including an extensive series of in-flight resting and exercise echocardiograms. The PI monitors all in-flight echoes remotely in real-time, and he and his colleagues at the Cleveland Clinic serve as the echocardiographic core lab for this study. We thus are in a unique position to guide on-flight acquisition as well as perform detailed examination of the ultrasound studies received. However, ICV was initially proposed in 1999 with echocardiographic techniques that are now over ten years old, focusing mainly on ventricular size, mass, and simple measures of systolic function, such as ejection fraction and stroke volume. Echocardiography has advanced considerably since then in the sophisticated ventricular mechanical data that can be extracted from ultrasound data. In the current proposal, we wish to validate extraction of these novel echocardiographic indices of ventricular mechanics (two-dimensional strain and torsion, among others) from the in-flight data acquired on the 10-year-old HDI-5000 ultrasound system aboard the International Space Station, which was never designed to provide such data. Once validated, we will be able to derive detailed regional ventricular mechanics from all of our in-flight studies, allowing direct comparison with the pre- and post-flight examinations to gain a much better understanding of the magnitude and time course of structural and functional changes in the cardiovascular system in microgravity.

These enhanced data from ICV will provide the ideal input for mathematical modeling of the cardiovascular system in space. The PI and colleagues have long experience with mathematical modeling ranging from lumped parameter models to 2D structural models to full 3D finite element models. We will apply the structural and strain data from ICV to our evolving numerical models of the cardiovascular system. To model atrophy of the heart, we will use the actual astronaut geometry from pre- and post-flight examinations, to build realistic 3D finite element models. Chamber behavior will be extracted for use in our less computationally intense lumped parameter model. Such modeling will be made available to the NASA community to enhance the comprehensive Digital Astronaut model.

Finally, looking toward a future of long duration missions to the moon and on to Mars, we anticipate that even more sophisticated ultrasound data will be available through the expected commercial development of hand-held three-dimensional echocardiographs. Our group stands in a unique position to capitalize on these developments and to validate their eventual use in the manned space program. For all of these reasons, we believe this proposal is quite responsive to the charge to the Cardiovascular Alterations Team.

Research Impact/Earth Benefits: Several aspects of this project are already generating significant real-world benefits with many more anticipated in the future. Our work attempting to harmonize strain measurements across platforms has pointed out intervendor variability that significantly limits penetration of strain echocardiography into clinical practice. To address this, I have (in my role of President of the American Society of Echocardiography) convened a task force in collaboration with the European Association of Echocardiography and technical representatives from multiple vendors (GE, Siemens, Philips, Toshiba, Esaote, Ziosoft, Zonare, among others). We have proposed a multipronged validation protocol, consisting of synthetic datasets, animal experiments, and clinical validation at upcoming international congresses. In addition, we have engaged the DICOM (Digital Imaging and Communications in Medicine) committee with 2 proposals: 1) development of a new standardized format for storing raw ultrasound data (ideal for strain measurements) and 2) development of standardized nomenclature for advanced mechanics parameters, so analysis packages of the various vendors can communicate their results with each other and between data and picture archives. Additionally, the modeling work being done in Cleveland and Auckland, while designed to allow simulation of the impact of physiological stressors in space flight on the cardiovascular system, will have widespread applicability in cardiology. For example, the user interface developed in Auckland allows any DICOM echocardiogram to be read into the program, segmentation and strain analysis to be performed, and then modeling of that heart using pre-existing fiber models of the ventricle. Once refined and validated, this should allow analysis of patients with regional and global dysfunction, as well as those with valvular heart disease. Work is also underway to allow 3D echoes to be read directly into the interface, including the full strain tensor as reported throughout the 3D space (Toshiba machine). Finally, we have leveraged our work in 3D echocardiographic strain to participate in an international consortium to establish normal values for global and regional 3D strain. 3D echocardiography is undergoing rapid development and this work will help to set normative standards against which clinical acquisitions can be compared.

Task Progress & Bibliography Information FY2012 
Task Progress: Task 1: Strain validation manuscript has been submitted to Journal of the American Society of Echocardiography following featured presentations at ACC (American College of Cardiology) 2011 and ASE (American Society of Echocardiography) 2011. Analysis of DICOM images yields lower absolute global (GLS) and regional (RLS) longitudinal strain values compared to source polar images. GLS from DICOM images has comparable reliability & reproducibility as from the source Polar images. Both methods of strain analysis are independently reliable; however, strain values from Polar & DICOM analyses are not interchangeable.

Task 2: An interim analysis from the effect of microgravity on myocardial strain was presented at ASE 2012 using pre-, in-, and post-flight data from 6 astronauts (49±4yr), median space stay 166 days. Pre- and post-flight images by experienced sonographers on earth and images in space acquired by the astronauts who had echo training before spaceflight (with real-time guidance of groundbased investigators). Strain data was assessed using a generalized mixed model in three different conditions (pre-, in- and post-flight). In this early analysis, there appears to be reduction in absolute GLS during flight, with normalization post-flight. Whether this is reflective of loading changes, inotropic alterations, or actual reduction in contractility will be topics for investigation in this on-going study.

Task 3: (A) Integrated cardiac function model: A semi-automated system allows ultrasound images to be segmented and fitted to a 3D+t finite-element mesh of the left ventricle. The segment boundaries are tracked using speckle tracking and the motion is encoded onto a geometrically accurate left ventricular mesh. Strain results are based on the mesh deformation and mesh and analysis data are integrated into the standard DICOM format and consequently into the PACS workflow. In progress: 1) Compare, validate, and update the software to build meshes that are quantitatively similar to segmenting and fitting MRI data; 2) Integrate software into subject diagnosis and reporting workflow; and 3) create software as a service based framework for integrating acquisition, segmentation, fitting, and analysis under development. (B) Orthotropic 3D Finite Element Heart Model: Local & global validation of the passive cardiac model, together with the development of the active systolic force generating cardiac model were completed. Parametric simulations were performed to predict the impact of gravity on LV stress and strain distributions in reduced gravity and numerical results were processed and analyzed to see whether the magnitude and location of the extreme end-diastolic stress and strain values change between the Earth and the space environments.

Task 4: To begin assessment of 3D strain acquisitions, we have implemented a protocol using the GE Vivid E9 to acquire both 2D and 3D strain in a variety of clinical patients. Early analysis suggests slight underestimation of longitudinal strain by 3D, likely related to lower frame rate.

Bibliography Type: Description: (Last Updated: 04/09/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Kassemi M, Iskovits I, Thomas JD. "Impact of Microgravity and Partial Gravity on Cardiac Shape." 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012.

2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. , Feb-2012

Awards Thomas JD. "Hearts in Space Symposium at the American Society of Echocardiography Annual Meeting, July 2012." Jul-2012
Papers from Meeting Proceedings Iskovitz I, Kassemi M, Thomas JD. "Impact of Microgravity and Partial Gravity on Cardiac Shape." 42nd International Conference on Environmental Systems, San Diego, CA, July 15-19, 2012.

42nd International Conference on Environmental Systems, San Diego, CA, July 15-19, 2012. AIAA paper AIAA-2012-3447. http://dx.doi.org/10.2514/6.2012-3447 , Jul-2012

Project Title:  Impact of Long Duration Space Flight on Cardiac Structure and Function Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 05/01/2010  
End Date: 09/30/2014  
Task Last Updated: 10/12/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Thomas, James David M.D. / The Cleveland Clinic Foundation 
Address:  Cardiovascular Medicine 
9500 Euclid Ave 
Cleveland , OH 44195-0001 
Email: thomasj@ccf.org 
Phone: 216-445-6312  
Congressional District: 11 
Web:  
Organization Type: NON-PROFIT 
Organization Name: The Cleveland Clinic Foundation 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Popovic, Zoran  The Cleveland Clinic Foundation 
Bungo, Michael  University Of Texas, Houston 
Martin, David  Wyle Laboratories, Inc. 
Greenberg, Neil  The Cleveland Clinic Foundation 
Borowski, Allen  The Cleveland Clinic Foundation 
Levine, Benjamin  The University of Texas Southwestern Medical Center at Dallas 
Kassemi, Mohammad  NASA Glenn Research Center 
Project Information: Grant/Contract No. NCC 9-58-CA02203 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02203 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
Human Research Program Gaps: (1) CV01:What are the in-flight alterations in cardiac structure and function?
Task Description: As astronauts venture farther into space, the impact of long-term microgravity on cardiovascular function may become a critical limitation to mission safety and success. In order to better understand the impact of long-term spaceflight on the structure and function of the heart, the PI is already involved in echocardiographic analysis of the most detailed study of the heart in space ever undertaken. Unfortunately, the echocardiograph on the International Space Station is more than a decade old and does not provide contemporary information on cardiac function, such as strain (the best measure of regional and global contraction of the muscle) and torsion (the twisting motion of the heart that links the pumping and filling functions of the ventricle). Our first task in this proposal is to develop and validate methodology to extract strain and torsion from space station echoes and then combine it with the numerous pre- and post-flight studies that will be conducted over the next four years. From these data, we will have a comprehensive view of the heart in space, information which will be integrated into evolving mathematical models of the heart that the PI and collaborators have developed, and which will be made available to the general NASA community via integration into the Digital Astronaut project. Finally, the PI and colleagues are involved extensively in the development of the next generation of echo machines and have the unique opportunity to develop and validate advanced applications for space use. We will focus on massively parallelized echo machines capable of real-time 3D imaging with automated volume measurements and comprehensive 3D strain and torsion analysis. As these machines become smaller over time, they will provide the ideal diagnostic tool for future space missions, be they to low earth orbit, a Lagrangian point, the moon, or even Mars.

Exposure to microgravity induces short and long-term changes in the cardiovascular system, with cardiac atrophy, orthostatic hypotension and impaired thermoregulation being the most recognizable. The most obvious issue, noted in the majority of astronauts after long-term space flight, is orthostatic hypotension. While its importance is clear, the etiology remains uncertain, with proposed mechanisms including hypovolemia, impaired baroreflexes, and left ventricular atrophy leading to systolic and/or diastolic dysfunction. In order to better define these issues, NASA is currently conducting Flight Study E377, "Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capacity, and Risk of Cardiac Arrhythmias" (Ben Levine and Mike Bungo, Co-PIs, both of whom are Co-Is on this application). This program is also termed the Integrated Cardiovascular Study, or ICV.

As part of this investigation, detailed imaging studies are conducted on astronauts before, during and after space flight, including an extensive series of in-flight resting and exercise echocardiograms. The PI monitors all in-flight echoes remotely in real-time, and he and his colleagues at the Cleveland Clinic serve as the echocardiographic core lab for this study. We thus are in a unique position to guide on-flight acquisition as well as perform detailed examination of the ultrasound studies received. However, ICV was initially proposed in 1999 with echocardiographic techniques that are now over ten years old, focusing mainly on ventricular size, mass, and simple measures of systolic function, such as ejection fraction and stroke volume. Echocardiography has advanced considerably since then in the sophisticated ventricular mechanical data that can be extracted from ultrasound data. In the current proposal, we wish to validate extraction of these novel echocardiographic indices of ventricular mechanics (two-dimensional strain and torsion, among others) from the in-flight data acquired on the 10-year-old HDI-5000 ultrasound system aboard the International Space Station, which was never designed to provide such data. Once validated, we will be able to derive detailed regional ventricular mechanics from all of our in-flight studies, allowing direct comparison with the pre- and post-flight examinations to gain a much better understanding of the magnitude and time course of structural and functional changes in the cardiovascular system in microgravity.

These enhanced data from ICV will provide the ideal input for mathematical modeling of the cardiovascular system in space. The PI and colleagues have long experience with mathematical modeling ranging from lumped parameter models to 2D structural models to full 3D finite element models. We will apply the structural and strain data from ICV to our evolving numerical models of the cardiovascular system. To model atrophy of the heart, we will use the actual astronaut geometry from pre- and post-flight examinations, to build realistic 3D finite element models. Chamber behavior will be extracted for use in our less computationally intense lumped parameter model. Such modeling will be made available to the NASA community to enhance the comprehensive Digital Astronaut model.

Finally, looking toward a future of long duration missions to the moon and on to Mars, we anticipate that even more sophisticated ultrasound data will be available through the expected commercial development of hand-held three-dimensional echocardiographs. Our group stands in a unique position to capitalize on these developments and to validate their eventual use in the manned space program. For all of these reasons, we believe this proposal is quite responsive to the charge to the Cardiovascular Alterations Team.

Research Impact/Earth Benefits: Several aspects of this project are already generating significant real-world benefits with many more anticipated in the future.

Our work attempting to harmonize strain measurements across platforms has pointed out intervendor variability that significantly limits penetration of strain echocardiography into clinical practice. To address this, I have (in my role of President of the American Society of Echocardiography) convened a task force in collaboration with the European Association of Echocardiography and technical representatives from multiple vendors (GE, Siemens, Philips, Toshiba, Esaote, Ziosoft, Zonare, among others). We have proposed a multipronged validation protocol, consisting of synthetic datasets, animal experiments, and clinical validation at upcoming international congresses. In addition, we have engaged the DICOM (Digital Imaging and Communications in Medicine) committee with 2 proposals: 1) development of a new standardized format for storing raw ultrasound data (ideal for strain measurements) and 2) development of standardized nomenclature for advanced mechanics parameters, so analysis packages of the various vendors can communicate their results with each other and between data and picture archives.

Additionally, the modeling work being done in Cleveland and Auckland, while designed to allow simulation of the impact of physiological stressors in space flight on the cardiovascular system, will have widespread applicability in cardiology. For example, the user interface developed in Auckland allows any DICOM echocardiogram to be read into the program, segmentation and strain analysis to be performed, and then modeling of that heart using pre-existing fiber models of the ventricle. Once refined and validated, this should allow analysis of patients with regional and global dysfunction, as well as those with valvular heart disease. Work is also underway to allow 3D echoes to be read directly into the interface, including the full strain tensor as reported throughout the 3D space (Toshiba machine).

Finally, we have leveraged our work in 3D echocardiographic strain to participate in an international consortium to establish normal values for global and regional 3D strain. 3D echocardiography is undergoing rapid development and this work will help to set normative standards against which clinical acquisitions can be compared.

Task Progress & Bibliography Information FY2011 
Task Progress: Task 1: Strain validation is ongoing but comparisons of Polar (EchoPAC) vs DICOM (Velocity Vector Imaging, VVI) data have been performed and shown at ACC 2011 (American College of Cardiology; featured abstract with press release) and ASE 2011 (American Society of Echocardiography; featured oral presentation). Work on regional strain validation has been accepted for presentation at the AHA2011 Conference. Validation project extension has been approved by IRB to exam pediatric population as well. Goal: Analyze > 100 studies, with manuscript submission by year's end. Customized software has been created to run validation statistics in a semi-automated fashion. Interplatform analysis of strain data is ongoing comparing these ultrasound modalities: GE Vivid 7, Philips HDI5000, and Philips iE33.

Task 2: All 2D and Doppler parameters have been measured for pre-, in-, and post-flight studies for all enrolled subjects (>10,000 measurements). There are insufficient subjects enrolled at this time to perform hypothesis testing, but interim analysis for safety has shown no areas of concern (e.g., ejection fraction varied from 65.2+/-5.6% preflight to 64.0+/-6.7% inflight to 67.7+/-4.4% postflight). 3D and advanced mechanics measurements are on-going.

Task 3: Completed software to segment ultrasound images and fit a finite-element mesh to the left ventricle. From an ApLAx view, the software segments and fits a mesh, subject to user verification, in a vendor independent manner from DICOM images. Strain analysis is based on mesh deformation. Embedding muscle-fibre structure allows fiber strain to be calculated. Presented Poster and Oral Abstract at American Society of Echocardiography 2011 Annual Conference.

For the actual modeling, a rigorous orthotropic material model was developed to capture the nearly incompressible cardiac tissue together with the nonlinear elastic characteristics of the muscle fibers and laminae. To simulate the structural response of the heart at end-diastole in 1g and microgravity, this orthotropic model was incorporated into a comprehensive 3D finite element structural model of the heart, based on fiber and laminae sheet architecture of the left and right ventricles provided by P. Hunter's group at University of Auckland. The model was implemented into the finite element code, ADINA, validated on a global level against intact whole heart in-vitro pressure-volume inflation data, and then used to predict and assess the impact of the gravitational field on the shape of the heart at end-diastole. The effect of gravity on the sphericity of the heart (ratio of LV long to short axis) has been shown for the different gravitational levels of Earth, Moon, Mars, and orbiting spacecraft (see uploaded file).

Task 4: To begin assessment of 3D strain acquisitions, we have implemented a protocol using the GE Vivid E9 to acquire both 2D and 3D strain in a variety of clinical patients. Early analysis suggests slight underestimation of longitudinal strain by 3D, likely related to lower frame rate.

Bibliography Type: Description: (Last Updated: 04/09/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Gladding P, Anwar S, Negishi K, Popovic Z, Hussan JR, Marwick T, Hunter P, Kassemi M, Levine B, Thomas JD. "Modeling the heart from echocardiographic strain data, collected on the International Space Station." ACC.11. 60th Annual Scientific Session of the American College of Cardiology, New Orleans, LA, April 2-5, 2011.

Journal of the American College of Cardiology 2011 Apr 5;57(14 Suppl):E1255. , Apr-2011

Abstracts for Journals and Proceedings Gladding P, Anwar S, Negishi K, Popovic Z, Odabashian J, Hussan J, Marwick T, Hunter P, Kassemi M, Levine B, Thomas JD. "Modeling the Heart in Space From Echocardiographic Strain Data Collected on the International Space Station." ASE2011. 22nd Annual Scientific Sessions of the American Society of Echocardiography, Montreal, Canada, June 11-14, 2011.

Journal of the American Society of Echocardiography 2011 May;24(5). , May-2011

Articles in Peer-reviewed Journals Kassemi M, Deserranno D, Thomas JD. "Incorporation of Cell-Level Myofilament Dynamics and Micro-fiber Cardiac Architecture in a Multi-Scale Finite Element Model of the Heart." Journal of Computational Physics, Special Issue: Multi-scale Modeling and Simulation of Biological Systems. In press, August 2011. , Aug-2011
Articles in Peer-reviewed Journals Kassemi M, Iskovitz I, Thomas JD. "Finite Element Implementation and Validation of an Invariant-Based Orthotropic Model for Passive Cardiac Tissue Behavior." Computers & Structures. In press, August 2011. , Aug-2011
Articles in Peer-reviewed Journals Kassemi M, Iskovitz I, Thomas JD. "Impact of Gravity on End-Diastolic Cardiac Sphericity: Predictions of an Orthothropic Tissue Model." Journal of Biomechanical Engineering. In press, August 2011. , Aug-2011
Awards Thomas JD. "Featured abstract at ACC2011 (ACC.11. 60th Annual Scientific Session of the American College of Cardiology, New Orleans, LA, April 2-5, 2011) with press conference, April 2011." Apr-2011
Project Title:  Impact of Long Duration Space Flight on Cardiac Structure and Function Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 05/01/2010  
End Date: 04/30/2014  
Task Last Updated: 06/21/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Thomas, James David M.D. / The Cleveland Clinic Foundation 
Address:  Cardiovascular Medicine 
9500 Euclid Ave 
Cleveland , OH 44195-0001 
Email: thomasj@ccf.org 
Phone: 216-445-6312  
Congressional District: 11 
Web:  
Organization Type: NON-PROFIT 
Organization Name: The Cleveland Clinic Foundation 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Borowski, Allen  Cleveland Clinic Foundation 
Bungo, Michael  University Of Texas, Houston 
Greenberg, Neil  Cleveland Clinic Foundation 
Kassemi, Mohammad  Case Western Reserve University 
Levine, Benjamin  The University of Texas Southwestern Medical Center at Dallas 
Martin, David  Wyle Laboratories, Inc. 
Popovic, Zoran  Cleveland Clinic Foundation 
Project Information: Grant/Contract No. NCC 9-58-CA02203 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02203 
Project Type: FLIGHT 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
Human Research Program Gaps: (1) CV01:What are the in-flight alterations in cardiac structure and function?
Task Description: As astronauts venture farther into space, the impact of long-term microgravity on cardiovascular function may become a critical limitation to mission safety and success. In order to better understand the impact of long-term spaceflight on the structure and function of the heart, this project's principal investigator is already involved in echocardiographic analysis of the most detailed study of the heart in space ever undertaken. Unfortunately, the echocardiograph on the International Space Station is more than a decade old and does not provide contemporary information on cardiac function, such as strain (the best measure of regional and global contraction of the muscle) and torsion (the twisting motion of the heart that links the pumping and filling functions of the ventricle).

The first task in this project is to develop and validate methodology to extract strain and torsion from space station echocardiography and then combine it with the numerous pre- and post-flight studies that will be conducted over the next four years. From these data, the researchers will have a comprehensive view of the heart in space. This information will be integrated into evolving mathematical models of the heart developed by Thomas and his collaborators and will be made available to the NASA community via integration into the Digital Astronaut project. Finally, the researchers are involved extensively in the development of next-generation echocardiography machines and have the unique opportunity to develop and validate advanced applications for space use.

The project will focus on massively parallelized echocardiography machines capable of real-time 3-D imaging with automated volume measurements and comprehensive 3-D strain and torsion analysis. As these machines become smaller over time, they will provide the ideal diagnostic tool for future space missions, be they to low-Earth orbit, a Lagrangian point, the moon, or even Mars.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2010 
Task Progress: New project for FY2010.

Bibliography Type: Description: (Last Updated: 04/09/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2010